Tramadol (2-[(Dimethylamino) methyl]-1-(3-methoxy phenyl)cyclohexanol is a non-narcotic opioid analgesic which was first described in the 1960's (see UK Patent 997399). It was first marketed in Germany in 1977 and subsequently in various countries and by 1980 a total of 34 different tramadol formulations in immediate release oral and injectable form were on the market.
In 1996 controlled release preparations containing tramadol were introduced, for example TRAMUNDIN RETARD capsules of Mundipharma GmbH, IRAMAL LONG 100 tablets of Grünenthal GmbH and ZYDOL SR tablets of G D Searle & Co. Ltd. The only medical indication for which the various tramadol products are used is the treatment of moderate to severe pain.
It has been reported that the most-commonly occurring adverse side effects during treatment of pain with tramadol preparations are gastrointestinal upsets. Between one third and a half of patients suffer nausea and vomiting initially when started on tramadol pain therapy.
The most common functional GI disorders are irritable bowel syndrome and non-cardiac chest pain. It is estimated 15-20% of the general population are affected by IBS at some time.
Functional GI disorders are difficult to diagnose as they involve disrupted gastrointestinal function and do not present evidence of organic or physical disease. No routine tests are available to confirm a diagnosis of IBS. However, diagnostic evaluation is often carried out to exclude other potential causes such as colonic cancer or inflammatory bowel disease such as Crohn's disease or ulcerative colitis.
Functional GI disorders are defined and diagnosed by a group of symptoms. For instance, IBS is characterised by a combination of intermittent abdominal pain and diarrhoea, constipation or both; a, or the, principal symptom is pain, which often commences after eating and is relieved by defecation; abdominal distension (bloating) is common. Other symptoms include the passage of mucus and a feeling of incomplete defecation. Clinical studies have indicated that IBS is a disorder affecting the entire GI tract.
The symptoms in IBS are chronic, with remissions and relapse, which may be brought on by stress, food poisoning or changes in bowel flora produced by antibiotics, and they cause discomfort, which, depending on the severity of the disorder, can range from inconvenience to severe distress. For those with severe symptoms, IBS can cause a significant reduction in quality of life to the point where the condition is debilitating.
IBS is not caused by structural, biochemical or infectious abnormalities. Psychological factors have been thought to be important, and more recently specific food intolerances have been implicated.
Patients with IBS exhibit increased gut sensitivity, suggesting that at least part of the problem may be because the nerves that carry information from the gut to the brain, the afferent neurons, produce a response greater than that expected to be produced by the stimuli they have received, which results in non painful stimuli being perceived as painful (visceral hyperalgesia). Antidepressants are thought to affect pain sensation at the spinal level and are used in the treatment of IBS; the antidepressant imipramine was found to increase gut transit time.
IBS is also characterised by abnormal gut motility that is, increased or irregular muscular movement of the gut resulting in diarrhoea, constipation and spasms.
Therapies which are currently used depending on the symptoms presented include dietary fibres i.e. ispaghula husk; antidiarrhoeals such as loperamide; osmotic laxatives; antispasmodics such as hyoscamine and dicyclomine, and dietary supervision if food intolerance is suspected.
For patients with severe pain it is common for mebeverine (which acts on smooth muscle) to be prescribed. However, results are often disappointing and this may lead to the trial of many other remedies of uncertain value, such as antidepressants mentioned above; these are thought to block the transmission of pain signals from the gut to the brain and can sometimes be effective when taken at lower doses than those administered for the treatment of depression.
There is no currently, satisfactory treatment for functional GI disorders.